The primary goal of this research is to explore a new mechanism responsible for efficient gas exchange in the lungs. Efficient gas exchange can only occur if regional ventilation and blood flow are closely matched. Our current understanding of these basic mechanisms is inadequate to understand and develop more effective treatments for lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, acute lung in- jury, or bronchopulmonary dysplasia. In this project, we will utilize cryomicrotome imaging of rat lungs, which provides high-resolution information about lung anatomy and maps of regional ventilation and perfusion, to test our hypothesis that regional perfusion and ventilation are tightly matched through the shared geometries of the airway and vascular trees. The highly-automated computer-aided segmentation methods to be developed in this project will provide the ability to extract and segment the complex airway and pulmonary artery and vein trees from cryomicrotome imaging data of rat lungs. This will allow us a) to compare the conductances of paired airway and vascular segments to determine if they are similar and b) correlate the predicted terminal ventilation and blood flows based on geometric tree properties with those measured via the cryomicrotome images. Our investigations will provide new insights and a mechanistic understanding of how ventilation and perfusion are matched within the complex and interwoven distributions systems of the lung. In the long-term we expect that the gained knowledge, as well as the developed novel computer-aided analysis methods, will enable us to better understand and treat lung diseases like emphysema and pulmonary hypertension where the airway and vascular trees become dissociated and inefficient gas exchange creates significant morbidity and can be life-threatening. PUBLIC HEALTH RELEVANCE: This project will allow us to gain new knowledge about the fundamental mechanisms of efficient gas exchange in lungs based on an animal study by utilizing advanced imaging and computer-aided analysis methods. A better understanding of the regional matching between pulmonary ventilation and perfusion is fundamental to developing new treatments for lung diseases like chronic obstructive pulmonary disease (COPD).